DETERMINATION OF METFORMIN AND INSULIN EFFECT ON HEPATIC TRIGLYCERIDE CONTENT

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Fatty infiltration of the liver can occur by four distinct mechanisms: 1) increased flux of fatty acids to the liver; 2) increased synthesis of fatty acids in hepatocytes; 3) decreased hepatocyte secretion of fatty acids in the form of very-low-density-lipoprotein and; 4) decreased oxidation of fatty acids by hepatocytes. Animal models suggest that de novo synthesis of fatty acids plays a significant role in the accumulation of liver fat in the setting of insulin resistance. Importantly, the level of fatty acid synthesis in the liver is a function of circulating insulin levels, even in the setting of hepatocyte insulin resistance. One would expect that as insulin resistance worsens and insulin levels rise (either as a result of increased pancreatic islet cell output or supplementation with exogenous insulin), so to would the rate of hepatocyte fatty acid synthesis. This could potentially increase the liver fat content. Investigators in the study propose to examine the effect of two current standard care therapies for type 2 diabetes mellitus on liver fat content: metformin and insulin. Liver fat content will be assessed using proton magnetic resonance spectroscopy before and after 4 months of therapy. Subjects will be randomly assigned to one of the two medication to be studied and closely monitored for any drug-specific toxicities associated with their use.